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Drug Interactions between fluconazole and losartan

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

fluconazole losartan

Applies to: fluconazole and losartan

MONITOR: Coadministration with fluconazole may increase the plasma concentration of losartan but decrease that of its active carboxylic acid metabolite. The mechanism is fluconazole inhibition of CYP450 2C9, the isoenzyme that mediates the conversion of losartan to the metabolite. In healthy volunteers, fluconazole (200 mg once a day for 10 days) increased the steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of losartan (100 mg once daily) by 31% and 69%, respectively, compared to administration of losartan alone. In contrast, the Cmax and AUC of the active metabolite decreased 54% and 41%, respectively. Changes in pharmacodynamic effects, if any, were not evaluated in the study. However, since the active metabolite is 10 to 40 times more potent by weight than losartan and is responsible for most of the angiotensin II receptor antagonism that follows losartan treatment, the potential for diminished pharmacologic effect should be considered. Fluconazole had no effect on the pharmacokinetics of eprosartan, another angiotensin II receptor antagonist.

MANAGEMENT: If fluconazole is to be given for more than a few doses, patients should consider having blood pressure monitored more closely following initiation, discontinuation or change of dosage of fluconazole. Use of an alternative antifungal agent which does not inhibit CYP450 2C9 (e.g., itraconazole, ketoconazole, terbinafine) or another angiotensin II receptor antagonist such as eprosartan may be considered.

References

  1. Kazierad DJ, Martin DE, Tenero D, et al. "Fluconazole significantly alters the pharmacokinetics of losartan but not eprosartan." Clin Pharmacol Ther 61 (1997): 203

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Drug and food interactions

Moderate

losartan food

Applies to: losartan

GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion. Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.

MONITOR: Grapefruit juice may modestly decrease and delay the conversion of losartan to its active metabolite, E3174. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The clinical significance is unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Patients who regularly consume grapefruits and grapefruit juice should be monitored for altered efficacy of losartan. Grapefruits and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact.

References

  1. "Product Information. Cozaar (losartan)." Merck & Co., Inc PROD (2001):
  2. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit 23 (2001): 369-73
  3. Ray K, Dorman S, Watson R "Severe hyperkalaemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction." J Hum Hypertens 13 (1999): 717-20

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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